The invention relates to antimicrobial and antiviral compositions containing an oxidizing species. The materials are made by reacting cooperating ingredients at controlled proportions to form an oxidant that can have a variety of end uses. The oxidizing species of the invention is an in situ generated oxidant stable for limited periods, typically less than a few days.
Peroxygen sanitizers and halogen sanitizers are known. Peroxygen sanitizers include compounds such as hydrogen peroxide, percarboxylic acids, percarbonates, perborates, etc. These materials are relatively well characterized and understood and are commonly used in a variety of end uses. Halogen sanitizers include compounds such as hypochlorite (HOCl), chlorine dioxide (ClO2), perchlorate (HClO4), perbromate (HBrO4), and others. These materials also have relatively well characterized compositions and properties. Halide and quaternary ammonium base sanitizers are also known. These materials are generally not considered oxidizing materials but provide sanitizing properties to materials. One type of halogen based sanitizers are sanitizers that can contain species such as I3xe2x88x921, IBrClxe2x88x921, and other similar species. Representative examples of such materials include Rembaum et al., U.S. Pat. No. 3,898,336; Rembaum et al., U.S. Pat. No. 3,778,476; Hollis et al., U.S. Pat. No. 4,960,590; Hollis et al., U.S. Pat. No. 5,093,078 and Dammann, European patent application No. 156646. These references describe isolated polymeric quaternary ammonium polyhalides based on synthetic polymeric ionene (known in the industry as polymeric quats), epi-amine, and cationic acrylamide polymer resins (containing 2 or more cationic groups) precipitated with polyhalogens. Similarly, Corby, U.S. Pat. No. 4,822,513; Corby, U.S. Pat. No. 5,047,164; and Corby, U.S. Pat. No. 5,202,047 describe mixed interhalogen salts limited to 4 halogens with a maximum of one iodine or bromine atom per complex. Also, Kramer et al., U.S. Pat. No. 4,941,989; and Kramer et al., U.S. Pat. No. 5,620,527 describe the use of antimicrobial compositions made of alkaline per-salts of quaternary ammonium compounds and hydroperoxide (i.e., HOOxe2x88x92) anions at pH""s of greater than 9.5. No polyhalide counterions are utilized. Asensio, EP 0 799 570 A1 discloses a five component antimicrobial mix containing two quaternary tri-iodides (prepared via conventional molecular halogen addition, not by in-situ reaction). LaZonby, et al., U.S. Pat. No. 5,658,467 describes the use of peracetic acid in combination with a non-oxidizing biocide for industrial process waters. Lastly, Wright et al., PCT Application No. WO 94/00548 describes non-halogen containing quaternary ammonium compounds which are used with peracids, preferably peracetic acid. This disclosure indicates that the peracid material is activated by the presence of the quaternary ammonium compound.
None of the aforementioned references teach the use of in-situ, labile antimicrobial compositions generated via halide salts and oxidants; especially peroxygen oxidants. A11 of these examples deal with stable, isolated antimicrobials that would remain in the application environment (e.g., food surface) indefinitely. Lastly, Wright et al., PCT Application No. WO 94/00548 describes non-halogen containing quaternary ammonium compounds which are used with peracids, preferably peracetic acid. This disclosure indicates that the peracid material is activated by the presence of the quat.
We have discovered a synergistic effect resulting from the combination of a source of quaternary or protonizable nitrogen, an oxidant, preferably a peroxygen compound, and a halide source, for example, an elemental halogen(s), or metal or ammonium halide salt(s), preferably including an iodide salt. More specifically, we have found that a synergistic oxidizing species is created from this combination. Since reaction is almost immediate, an in-situ aqueous or non-aqueous use solution can be available for use immediately after mixing as an antimicrobial or antiviral composition; or the active composition can be stabilized and post-incorporated into a non-aqueous liquid, gel, aerosol, powder, or solid formulation.
It is also possible to produce solid sanitizing substrates containing this oxidizing species that have residual antimicrobial and antiviral effectiveness; such as in air filters or as packaging or plastic or as cutting board additives.
Accordingly, the invention resides in a complex for antimicrobial or antiviral use, the complex being the product of an in-situ reaction of a source of a quaternary or protonizable nitrogen compound, an oxidant, and a halide source. The invention also resides in the use of said complex to reduce microbial or viral populations on a surface or object or in a body or stream of water. Thus, this in-situ species is effective in reducing microbial and viral populations on hard surfaces (such as glass, ceramics, metal, natural and synthetic rock, wood, and polymeric), elastomers and plastics, woven and non-woven substrates. More specifically, the compositions containing the complex are shown to be effective antimicrobial and antiviral agents for sanitizing and disinfecting surfaces and air streams typically encountered in hospital, surgical, infirmity, birthing, mortuary, and clinical diagnosis rooms. These surfaces can be those typified as xe2x80x9chard surfacesxe2x80x9d (such as walls, floors, bed-pans, etc.), or woven and non-woven surfaces (such as surgical garments, draperies, bed linens, bandages, etc.), or patient-care equipment (such as respirators, diagnostic equipment, shunts, body scopes, etc.), or a plethora of surgical and diagnostic equipment.
The complex can also be used to reduce odors and microbial or viral populations in gaseous streams, bleaching of or reducing microbial or viral populations on woven or non-woven substrates, and treating skin diseases of, or on, mammals; i.e., in treating skin diseases on animals (especially mammals), or those which spread via transfer to air or surface substrates, such as disease from fungi, bacteria and viruses. The complex can also be used to reduce microbes and odors in animal feeds, in animal watering stations and enclosures, in animal veterinarian clinics, animal surgical areas, and to reduce animal or human pathogenic (or opportunistic) microbes and viruses on animals. The complex can also be used to reduce opportunistic pathogenic microbes on living eggs.
Additionally, the compositions containing the complex are effective by themselves, or mixed with other adjuvants, in reducing microbial and viral populations in applications in the food industry. These include food preparation equipment, belt sprays for food transport lines, boot and hand-wash dip-pans, food storage facilities and anti-spoilage air circulation systems, aseptic packaging sanitizing, food refrigeration and cooler cleaners and sanitizers, warewashing sanitizing, blancher cleaning and sanitizing, food packaging materials, cutting board additives, third-sink sanitizing, beverage chillers and warmers, meat chilling or scalding waters, sanitizing gels, food processing antimicrobial garment sprays, and non-to-low-aqueous food preparation lubricants, oils, and rinse additives.
The invention also resides in a concentrated antimicrobial and antiviral species including in composition the product of an in-situ reaction of a source of quaternary or protonizable nitrogen, an oxidant, preferably a peroxygen compound, and a halide source. The reaction may be conducted in an aqueous, non-aqueous, gel, aerosol, or solid-phase or powdered media, and for each part by weight of the halide source there is about 0.1 to 30 parts by weight of the nitrogen compound, about 0.1 to 40 parts by weight of the oxidant compound. In an aqueous solution, the composition has a pH of less than about 9.5.
The invention further resides in an aqueous, in-situ, antimicrobial and antiviral composition containing the combination of: (a) a source of quaternary or protonizable nitrogen; (b) an oxidant, preferably a peroxygen compound; (c) a halide source, e.g., a metal or ammonium halide salt(s), halogens, or organo-halides; and (d) the balance being water. Preferably, for each part by weight of the halide source there is about (a) 0.1 to 80 weight percent (wt-%), preferably about 1 to 15 wt-%, of a source of a quaternary or protonizable nitrogen source (most preferably a quaternary ammonium, protonized amine, amine oxide, or amphoteric surfactant source); (b) about 0.1 to 75 wt-%, preferably about 1 to 20 wt-% of an oxidant (preferably a peroxygen) compound; and (d) the balance being water. In a diluted form, this use solution will contain about 0.1 to 200,000 parts per million (ppm), preferably 5 to 10,000 ppm, and most preferably 10 to 100 ppm of the halide source.
The invention further resides in a mixable, at the point of use, two-part liquid concentrate antimicrobial and antiviral composition having in one part: about 0.1 to 80 wt-% preferably about 1 to 15 wt-%, of a source of a quaternary or protonizable nitrogen compound, about 0.1 to 75 wt-%, preferably about 1 to 20 wt-%, of an oxidant, and the balance being water; and in the second part: about 0.1 to 80 wt-% of a halide source, preferably about 1 to 15 wt-%, and the balance being water. Various inerts and surfactants may be added to either part.
Also, the invention resides in an antimicrobial and antiviral composition suitable for subsequent incorporation into solid, gel, aerosol, or non-aqueous liquid cleaning, sanitizing, or disinfecting products for treatment of surfaces. Thus, these include in powder, liquid, gel, or solid form: a) a source, preferably a natural one, of a quaternary or protonizable nitrogen compound; (b) an oxidant, preferably a peroxygen compound or oxidizing gas; (c) a halide source; and optionally (d) a source of acidity; wherein for each part by weight of the halide source there is about 0.1 to 30 parts by weight of the nitrogen compound, about 0.1 to 40 parts by weight of the oxidant compound, unless an oxidizing gas is used to form the complex in-situ and, then, an excess of the oxidant can be employed. The antimicrobial or antiviral composition is incorporated into the cleaning, disinfecting, or sanitizing substrate at a level of about 0.001 to about 95 weight %.
The invention also resides in said powder antimicrobial or antiviral compositions suitable for incorporation (casting, absorbing, adsorbing, spray-drying, etc.,) into solid, elastomeric, or fibrous substrates for residual antimicrobial or antiviral effects.
The invention also resides in antimicrobial or antiviral compositions comprising a combination of (a) a quaternary or protonizable nitrogen compound, preferably a natural source, with (b) a polyhalogen-containing anion, and (c) a water-soluble or dispersible substrate which greatly improves the solubility or efficacy of said complexes.
The invention further resides in a process for preparing a solvent-free liquid, powdered, or solid-phase antimicrobial or antiviral complex including applying or generating heat, gaseous water vapor, or chemical hydrates, to a mixture of a solid, gel, or powder composition containing a source of a quaternary or protonizable nitrogen compound, an oxidant, and a halide source; and cooling the resulting complex to ambient temperature. It also encompasses solvent-free liquid complexes prepared by such a method.
The invention also resides in treating food processing or transport waters with said liquid, gel, solid, or powdered compositions.
The invention additionally resides in treating food processing equipment and/or ware, (e.g. utensils, dishware, washware,) with said liquid, gel, aerosol, solid, or powdered compositions, or solutions containing these compositions.
The invention additionally resides in sanitizing third-sink rinse waters and utensils (e.g. bar glasses) with said liquid, gel, solid, or powdered compositions.
The invention additionally resides in treating animal quarters, surgical or treatment areas, in animal feeds, or animal carcasses; with said compositions.
The invention additionally resides in treating air streams with said compositions.
The invention involves a complex for antimicrobial or antiviral use, including the product of the in-situ, i.e., in place, reaction of a source of quaternary or protonizable nitrogen, an oxidant, preferably a peroxygen compound and, a halide or halogen source, e.g., a metal or ammonium halide salt; wherein the reaction is conducted in an aqueous, non-aqueous, gel, aerosol, solid phase or powdered media. Preferably, for each part by weight of the halide source there is about 1 to 10 parts by weight of the source of quaternary or protonizable nitrogen, and about 1 to 10 parts by weight of the oxidant, preferably peroxygen compound. In an aqueous reacted solution, or in a use solution, the pH is about 9.5 or less.
The complex of the invention may be prepared from the in-situ reaction being carried out in water, a non-aqueous liquid, a gel, or aerosol. Alternately, another process lies in the in-situ reaction in a powder or solid state with water vapor or hydrating compounds present; while yet another process may be carried out with an oxidizing gas passing into the powder or solid or a non-aqueous liquid.
Typically, the quaternary nitrogen compound can be a quaternary ammonium compound having the formula: 
wherein X is an anion except a hydroperoxide anion, and R, Rxe2x80x2, Rxe2x80x3 and Rxe2x80x2xe2x80x3 are each independently a straight or branched, unsaturated or saturated, hydrocarbon group of 1 to 24 carbon atoms, in which the hydrocarbon chain is unsubstituted or substituted by hydroxyl, carboxyl, or alkylamido, or in which the hydrocarbon chain is uninterrupted or interrupted by a heteroatom; an aryl group, or aralkyl group in which alkyl has 1 to 4 carbon atoms. One embodiment of the formula I includes a compound where Rxe2x80x2 is benzyl and Rxe2x80x3 is aryl or benzyl.
An alkyl group is defined as a paraffinic hydrocarbon group which is derived from an alkane by removing one hydrogen from the formula. The hydrocarbon group may be linear or branched. Simple examples include methyl (CH3) and ethyl (C2H5). However, in the present invention, at least one alkyl group may be medium or long chain having, for example, 8 to 16 carbon atoms, preferably 12 to 16 carbon atoms.
An alkylamido group is defined as an alkyl group containing an amide functional group: xe2x80x94CONH2, xe2x80x94CONHR, xe2x80x94CONRRxe2x80x2.
A heteroatom is defined as a non-carbon atom which interrupts a carbon chain. Typical heteroatoms include nitrogen, oxygen, phosphorus, and sulfur.
An aryl group is defined as a phenyl, benzyl, or naphthyl group containing 6 to 14 carbon atoms and in which the aromatic ring on the phenyl, benzyl or naphthyl group may be substituted with a C1-C3 alkyl. An aralkyl group is aryl having an alkyl group of 1 to 4 carbon atoms.
Certain quaternary nitrogen compounds are especially preferred. These include alkyl trimethyl ammonium salts, dialkyl dimethyl ammonium salts, alkyl dimethyl piperidinium salts, and alkyl dimethyl pyridinium salts.
The nitrogen compound can also be of the formula: 
wherein X1 is an anion; and R10, R11 and R12 are each, independently, hydrogen or at least one straight or branched, saturated or unsaturated, hydrocarbon group of 1 to 24 carbon atoms, in which the hydrocarbon chain is unsubstituted or substituted by hydroxyl, carboxyl, or alkylamido, or in which the hydrocarbon chain is uninterrupted or interrupted by a heteroatom; an aryl group, or aralkyl group in which alkyl has 1 to 4 carbon atoms.
Several preferred compounds are shown below. The first structure shown is cetyl trimethyl ammonium chloride, which is an example of formula I; the second structure, dodecyl dimethyl ammonium hydrochloride, is an example of formula II, and the third is didecyl dimethyl ammonium chloride, another example of formula I: 
In each structure, the ammonium nitrogen is seen as covalently bonded to four substituents and ionically bonded to a chlorine anion.
In the invention, the quaternary ammonium cation can also be generated from an amphoteric molecule. An amphoteric compound can function as either an acid or as a base, depending on its environment, and has both functional groups present. A representative structure of the cation generated from an amphoteric molecule is shown below: 
wherein W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-6 carbon atoms;
Rb is R4xe2x80x94COxe2x80x94NH in which R4 is a saturated or unsaturated, branched or linear hydrocarbon group having 4-22 carbon atoms, or R4;
R1 is hydrogen, A or (A)nxe2x80x94Wxe2x80x94CO2xe2x88x92M+ in which A is a linear or branched alkyl, hydroxyalkyl or alkoxyalkyl having 1-4 carbon atoms, n is an integer from 0 to 6, and M is an alkali metal cation, a hydrogen ion or an ammonium cation;
R2 is (A)nxe2x80x94Wxe2x80x94CO2xe2x88x92M+;
R3 is hydrogen or A; and
X is an anion.
An example of a suitable amphoteric is shown below: 
where R is hydrogen, straight or branched alkyl having 1 to 16 carbon atoms, in which the alkyl group is uninterrupted or interrupted by phenyl. This is not itself a quaternary ammonium compound. Treatment with an organic or inorganic acid H+Xxe2x88x92 can result in a compound of the formula: 
where Xxe2x88x92 is an anion. This does indeed represent a quaternary ammonium compound which can be mixed with an appropriate oxidant and halogen, or halide salt, to meet the claimed invention, wherein.
Another class of amphoteric compounds can include the phosphorus containing species such as phospholipids like the lecithins (including phosphatidyl choline.), sphingomyelin, and the cephalins. Or modified phospho-amphoterics such as the Phosphoterics(copyright), sold by Mona Industries.
The invention can also use protonizable nitrogen sources. Examples include proteins, amino acids, amine oxides and amines which can form acid salts and mixtures thereof. These include, for example, sarcosine, taurine, glycine, and simple proteins such as albumins, phosphoproteins, protamines, histones, chromoproteins, schleroproteins, glutenins and globulins. Examples of protonizable proteins include milk, egg, blood and plant proteins. The nitrogen compound can be a protein, an acid salt thereof, or a mixture Of proteins and their corresponding acid salts. Generally, these can be characterized as: 
wherein Ra is a linear or branched, saturated or unsaturated, hydrocarbon, hydroxyalkyl or alkoxyalkyl group having 1 -22 carbon atoms; Rb is H or CH3, and W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-4 carbon atoms.
Rd is a common moiety as part of natural amino acids; e.g., H, alkyl, hydroxyalkyl, thioalkyl, alkyl-aryl, carboxyl, amido, alkyl-amino, and the like.
[poly-peptide]acidified+ refers to an acidified polypeptide, such as an acidified protein.
Additional preferred quaternary nitrogen sources include a choline, particularly a choline chloride, a choline bitartrate, an acetyl choline; or mixtures thereof. An additional preferred compound is cetyl dimethyl pyridinium chloride. The nitrogen source may also include mixtures thereof.
The nitrogen compound can also be a betaine, sultaine or phosphobetaine of the formula 
wherein Z is CO2H, CO2xe2x88x92, SO3H, SO3xe2x88x92, OSO3H, OSO3xe2x88x92, OPO3H or OPO3xe2x88x92; W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-6 carbon atoms; and
Ra is a linear or branched alkyl, hydroxyalkyl or alkoxyalkyl group having 1-22 carbon atoms; or R4xe2x80x94COxe2x80x94NH(CH2)xxe2x80x2 in which R4 is a saturated or unsaturated, branched or linear hydrocarbon group having 4-22 carbon atoms, and xxe2x80x2 is an alkylene group having 1-6 carbon atoms.
A suitable betaine cation is shown below: 
wherein; R is a linear or branched alkyl, hydroxyalkyl or alkoxyalkyl group having 1-22 carbon atoms; or R4xe2x80x94COxe2x80x94NH(CH)x in which R4 is a saturated or unsaturated, branched or linear hydrocarbon group having 4-22 carbon atoms, and x is an alkylene group having 1-6 carbon atoms. Of special interest is the natural product betaine where R has 1 carbon atom.
In another embodiment, the nitrogen compound can be of the formula: 
wherein R6, R7 and R8 are each, independently, H or xe2x80x94A1xe2x80x94Y in which A1 is a C7 to C20 saturated or unsaturated, linear or branched alkylene group, and Y is H, NH2, OH or COOM1, in which M1 is H or a Group I metal ion;
B is a C1 to C20 saturated or unsaturated, linear or branched chain alkylene group, and Y1 is H, NH2, OH, COOM2 or xe2x80x94NHxe2x80x94CORq in which M2 is H or a Group I metal ion and Rq is a C1 to C20 saturated or unsaturated, linear or branched chain alkyl group;
R5 is H or a C1 to C3 alkyl group at one of the nitrogen atoms; and
X1xe2x88x92 is an anion.
Typical imidazolines are: coconut hydroxyethyl imidazoline, tall oil aminoethyl imidazoline, oleyl hydroxyethyl imidazoline, the Miramines(copyright), the Rhodaquats(copyright), the Monazolines(copyright), the Rewoterics(copyright), the Crodazolines(copyright), available from Mona Industries Inc., Rhone Poulenc, Rewo Chemische Werke GmbH, and Croda Surfactants Ltd.
In addition to the source of quaternary or protonizable nitrogen, an oxidizing agent is also necessary. It is possible to utilize oxidants such as hypochlorites, chlorates, chlorites, permanganates, nitrates, or nitric acid, etc.; or gaseous oxidants such as ozone, oxygen, chlorine dioxide, chlorine, sulfur dioxide, etc. Preferred compounds include peroxides and various percarboxylic acids, including percarbonates. The preferred peroxygen compound is hydrogen peroxide, peracetic acid, or a percarbonate. The percarbonate can be formed in situ as a mixture of hydrogen peroxide and sodium bicarbonate. Percarboxylic acids may also be formed in situ by use of a combination of hydrogen peroxide and the desired carboxylic acid. For solid compositions, the use of percarbonates, perborates, persulfates, etc., are useful; especially where the backbone substrate (e.g., carbonate) itself is not essentially oxidized but instead acts as a substrate for the peroxygen complex. Most preferred is sodium percarbonate in solid formulations; however, gaseous oxidants are useful for non carbonate containing compositions. For liquid compositions, hydrogen peroxide or peracetic acid are the preferred oxidants; however, hypochlorites, chlorites, or ozone might also be employed for in-situ preparations. Ultimately, any oxidant that can convert the halide source into its complexed form is acceptable.
There are a large number of possible halide sources useful in the present invention such as metal or ammonium halides, haloforms or other organic halogens, or elemental halogens. Preferred metal halides include alkali metal iodide salts of the formula MIn, and MBrn wherein M is a metal ionic species and n is a number equal to the metal valence. Preferred alkali metals are sodium and potassium. Other preferred halides include bromides and chlorides. A preferred embodiment uses a metal halide salt which includes a mixture of halide salts containing at least one iodide salt. The alkali metal is preferably sodium or potassium. Another preferred embodiment uses a single metal halide salt which is an iodide or bromide salt. A preferred salt is potassium iodide, cuprous iodide or a mixture thereof. Also useful are sources containing halides such as sea water, kelp, table salt, etc.
The invention can also include, if necessary, an acid component for controlling the use solution pH. This may be necessary for non-permanent quaternary ammonium compounds (i.e., amphoteric, amine oxides, amines, proteins, amino acids) to enhance microbial reduction; probably because the unquaternized amine compound must be in its cationic or slightly neutralized form to form the labile, in-situ complex. The exact pH necessary will depend on the identity of the amine involved but, preferably, should be about 9.5 or less, preferably less than about 8.5.
Mineral and organic acids are useful for pH adjustment. The acid source might, for example, be an inorganic-based acid such as phosphoric, sulfuric, hydrochloric, nitric, sulfamic; or organic-based such as malic acid, tartaric acid, citric acid, acetic acid, glycolic, glutamic acid, sorbic acid, benzoic acid, succinic acid, or dimer and fatty acids; or mixtures thereof. Alternatively, the source of acidity can include an acid salt such as sodium diacetate, monobasic potassium or sodium phosphate. Additionally, carbonation acidification via the interaction of carbon dioxide with water is possible for aqueous formulations.
Besides the aforementioned cationic and amphoteric surfactants for the active complex formation, the invention also includes standard nonionic, anionic, cationic, or amphoteric compounds for surface tension reduction, wetting, and detersiveness. For example, linoleic acid, alkyl glycosides, alcohol ethoxylates, nonylphenol ethoxylates, alkanolamides, alkylbenzene sulfonates, petroleum sulfonates, diphenylether sulfonates, alpha-olefin sulfonates, stearyl citrate, alkyl naphthalene sulfonates, Pluronics(copyright) and various short-chain fatty acids are all readily useful. The wetting agents are typically not necessary for affecting the microbial reduction, but are present for detersive and surface tension reduction reasons; however, some may be employed as part of the synergistic, in-situ, antimicrobial formula.
Likewise, inerts might be added as fillers, buffers, chelants, anticaking agents, etc. For example, formulations have been prepared with: sodium chloride, bicarbonates, sulfates, silicates, phosphates, cellulosic derivatives, and EDTA.
It is believed that the working compound in the composition of the invention is a poly-halogen salt of the quaternary ammonium cation. The poly-halogen salt can include an anion of the formula IwBryCly1Fz, wherein w is an integer from 1 to 8, y and y1, are each independently integers from 0 to 8, and z is an integer from 0 to 1. In a typical reaction, for example, a quaternary ammonium compound reacts with potassium iodide in the presence of an oxidizing agent to produce the poly-halogen salt. If only KI is used, the poly-halogen anion is represented by Iw, where w ranges from 1 to 8. If KBr is also added to the reaction mixture, the resulting interhalogen anion is represented by IwBry, where w plus y equals 2 to 9. If a quaternary ammonium chloride is used the reaction with potassium iodide in the presence of an oxidizing agent would produce an inter-halogen salt; however, in contrast to other known interhalogens containing three or less halogen atoms the current art contains 4 or more. While an inorganic metal bromide is optional in the reaction mixture, the inorganic metal or ammonium iodide is not. The product requires the presence of at least some inorganic metal or ammonium iodide.
The aqueous solution of the invention, made by the in-situ reaction or by addition of the pre-made complex to a solution, is characterized by a yellow to red color which serves as an indicator of solution effectiveness. As long as the color remains, the solution retains good killing properties. The effective time period is about 50 hours. Generally for unbuffered or non-acidic formulations, as the reaction takes place, the pH of the solution increases from about 5 to about 10. At the same time, the oxidation/reduction potential (ORP) increases accordingly. This is noteworthy since ORP normally is in inversely proportional to pH and, thus, indicates a very active oxidizing species being formed. According to the claimed invention, use solutions are aqueous solutions containing a source of quaternary or protonizable nitrogen ammonium compound, an oxidant which is preferably a peroxide compound, a metal or ammonium halide and any resulting reaction products. It has been discovered that the preferred ternary ratio between the three added ingredients, the quaternary or protonizable nitrogen ammonium compound, the oxidant which is preferably a peroxide, and the halide source, e.g. metal or ammonium halides, respectively can range from 1:11 to 1:5:1 to 1:15:15. An optimal range is 1:3:1 to 1:3:3.
Use solutions are formed by combining, in an aqueous medium, the individual components consisting of a quaternary ammonium compound, a peroxygen compound and a metal halide. Reaction is virtually instantaneous, resulting in a use solution which can be used almost immediately. Alternately, the use solution can be formed by incorporating the pre-made complex into a solution. The use solution can be utilized in any application needing either antimicrobial or oxidizing efficacy.
The antimicrobial compositions of the invention are either solid-phase, powdered, gels, aerosols, non-aqueous liquids, or 2-part liquid mixtures which can be added to an aqueous rinse or wash liquid or a non-aqueous (e.g., mineral oil, lecithin) formulation.
The invention includes a process for preparing a solvent-free liquid, gel, aerosol, powder, or solid antimicrobial or antiviral complex including applying or generating heat, gaseous water vapor, or chemical hydrates, to a mixture of a solid, gel, or powder composition having a source of a quaternary or protonizable nitrogen compound; an oxidant; a halide source; and cooling the resulting complex to ambient temperature. In one embodiment, the mixture is heated in an extruder or hot-melt apparatus. Optionally, heat is applied or generated to a temperature above 30xc2x0 C.
The invention further includes a process for preparing antimicrobial and antiviral compositions suitable for subsequent incorporation into solid, gel, aerosol, or non-aqueous liquid cleaning, sanitizing, or disinfecting products for treatment of surfaces. Thus, these include in powder, liquid, gel, or solid form: a) a source, preferably a natural one, of a quaternary or protonizable nitrogen compound; (b) an oxidant, preferably a peroxygen compound or oxidizing gas; (c) a halide or halogen source; and optionally (d) a source of acidity; wherein for each part by weight of the halide source there is about 0.1 to 30 parts by weight of the nitrogen compound, about 0.1 to 40 parts by weight of the oxidant compound, unless an oxidizing gas is use to form the complex in-situ and, then, an excess of the oxidant can be employed. The antimicrobial or antiviral composition is incorporated into the cleaning, disinfecting, or sanitizing substrate at a level of about 0.001 to about 95 weight %.
The invention also includes a process for making powder antimicrobial or antiviral compositions suitable for incorporation (casting, absorbing, adsorbing, spray-drying, etc.,) into solid, elastomeric, or fibrous substrates for residual antimicrobial or antiviral effects.
The invention also resides in a process for preparing antimicrobial or antiviral compositions comprising a combination of (a) a quaternary or protonizable nitrogen compound, preferably a natural source, with (b) a polyhalogen-containing anion, and (c) a water-soluble or dispersible substrate which greatly improves the solubility or efficacy of said complexes.
The antimicrobial solutions used in treating said surfaces typically have, for solid compositions, about 0.1 to 400 grams of antimicrobial composition per liter of water, preferably about 1 to 100 grams per liter, and most preferably about 2 to 30 grams per liter.
The two part liquid concentrate of the invention can also be used in the above situations. Preferably, the two part concentrate is mixed to provide a dilute aqueous solution of about 0.1 to 130,000 ppm of the total concentrate; wherein the surfaces are treated with the dilute aqueous solution.
The invention includes a number of antimicrobial and antiviral methods and processes. The invention can be found in a method of reducing microbial or viral populations on a surface or object; said method including treating said surface or object with an aqueous solution of an effective amount of a complex resulting from an in-situ reaction of a source of a quaternary or protonizable nitrogen compound, an oxidant, and a halide source. In one embodiment, the surface is a clean-in-place (CIP) system, while in another it is one of the many non-CIP surfaces encountered in preparing food (e.g., cutting boards, sinks, ware-wash systems, utensils, counter tops, transport belts, aseptic packaging, boot and hand-wash dip-pans, food storage facilities and anti-spoilage air circulation systems, food refrigeration and coolers, blanchers, food packaging materials, third-sink containers, etc.).
In yet another the surface is in a hospital, environment and are sanitized or disinfected surfaces in surgical, infirmity, birthing, mortuary, and clinical diagnosis, etc., rooms. These surfaces can be those typified as xe2x80x9chard surfacesxe2x80x9d (such as walls, floors, bed-pans, etc.,), or woven and non-woven surfaces (such as surgical garments, draperies, bed linens, bandages, etc.,), or patient-care equipment (such as respirators, diagnostic equipment, shunts, body scopes, etc.,), or a plethora of surgical and diagnostic equipment. Also, the medical-related surfaces might be those of medical waste or blood spills. The microbes and viruses are often those which lead to tuberculosis, HIV, hepatitis"", herpes"", and other human pathogenic or opportunistic entities by physical contact or air transmission. The skin disease in question can be, for example, athletes foot fungus or hairy hoof wart disease. Alternatively, the disease can be a skin or transmittable viral disease such as parvovirus, coxsackie or herpes. The disease can also be a mycobacterial or bacterial type, such as tuberculosis or Legionella.
These compositions can also be used to reduce microbial and viral counts in air and liquids by incorporation into filtering media or breathing filters.
The invention also includes a method of reducing microbial or viral populations in a body or stream of water including treating said body or stream with an effective amount of a complex resulting from an in-situ reaction of a source of a quaternary or protonizable nitrogen compound, an oxidant, and a halide source. The body of water can be a swimming pool or a cooling tower, or can alternatively include food processing waters (e.g., flumes, can warmers, retort waters, third-sink sanitizing, bottle coolers, food sprays and misting systems, etc.,). beverage chillers and warmers, meat chilling or scalding waters, sanitizing gels, food processing antimicrobial garment sprays, and non-to-low-aqueous food preparation lubricants, oils, and rinse additives.
The complex resulting from an in-situ reaction of a source of a quaternary or protonizable nitrogen compound, an oxidant, and a halide source can also be used to reduce odors and microbial or viral populations in gaseous (especially air) streams by passing said aqueous streams through a bed, or woven or non-woven substrate or filter, including said complex. The complex can also be used for bleaching or reducing microbial or viral populations on woven or non-woven substrates, like linens or garments, by treating said substrate with an aqueous solution including the complex.
Skin diseases ofxe2x80x94or on, or transmittablexe2x80x94mammals can also be treated with the same complex. Especially useful is the treatment of skin diseases on animals, or those which spread via transfer to air or surface substrates, such as diseases from fungi, bacteria and viruses. These spreadable skin diseases can include athletes foot fungus and hairy hoof wart disease, or one of the many organisms leading to Mastitis or other mammalian milking diseases. The disease can be a viral disease such as parvovirus, coxsackie virus, or herpes virus. The disease can also be bacterial, such as S. aureus, E. coli, Streptococci, etc., or a Mycobacterium type such as that leading to tuberculosis.
These compositions can also be used to reduce microbial and viral counts in air and liquids by incorporation into filtering media or breathing filters. Especially useful is for removal of water and air-born pathogens such as Legionella.
The same complex can be used in reducing microbes and odors in animal feeds and in animal watering stations, enclosures, in animal veterinarian clinics, animal inspection areas, animal surgical areas. Reductions in human pathogenic microbes on animals can be obtained by applying to said animals an aqueous solution, or non-aqueous solution or gel, of an effective amount of the complex. Finally, the complex can be used to reduce opportunistic pathogenic microbes on eggs, by applying to said eggs an aqueous solution of an effective amount of the complex; especially chicken eggs.
The present invention also includes as an alternative embodiment a two part liquid concentrate where each part contains an aqueous concentrate including a nitrogen source, an oxidant compound, preferably a peroxygen compound and optionally an acidity source in part (a) and a metal halide in part (b); and optionally, inerts and wetting agents.
Typical two part liquid formulation ranges are:
When used, a total actives concentration ranging from 10 to 100,000 ppm is preferred. Useful product use concentration ranges for sanitizing with either a liquid or solid composition are given in the table below:
The composition of the invention may also contain one or more rheology modifiers, to enhance viscosity, or thicken and cause the aqueous treatment to cling to the surface being treated. Clinging enables the composition to remain in contact with the transient and resident pathogenic bacteria for longer periods of time, thereby promoting microbiological efficacy and resisting waste because of excessive dripping. The rheology modifier may be a film former or may act cooperatively with a film forming agent to form a barrier that provides additional protection.
Preferred rheology modifiers include colloidal aluminum silicate, colloidal clays, polyvinyl pyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyalkylene oxides, polyacrylamides, or mixtures thereof.
Water soluble or water dispersible rheology modifiers that are useful can be classified as inorganic or organic. The organic thickeners can further be divided into natural synthetic polymers with the latter still further subdivided into synthetic natural-based synthetic petroleum-based.
Organic thickeners are generally compounds such as colloidal magnesium aluminum silicate (Veegum), colloidal clays (Bentonites), or silicas (Cab-O-Sils) which have been fumed to create particles with large surface size ratios.
Natural hydrogel thickeners of use are primarily vegetable derived exudates. For example, tragacanth, karaya, and acacia gums; and extractives such as caragheenan, locust bean gum, guar gum and pectin; or, pure culture fermentation products such as xanthan gum are all potentially useful in the invention. Chemically, all of these materials are slats of complex anionic polysaccharides. Synthetic natural-based thickeners having application are cellulosic derivatives wherein the free hydroxyl groups on the linear anhydro-glucose polymers have etherified or esterified to give a family of substances which dissolve in water and give viscous solutions. This group of materials includes the alkyl and hydroxyalkylcelluloses, specifically methylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethycellulose, hydroxyethylcellulose, ethylhydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic petroleum-based water soluble polymers are prepared by direct polymerization of suitable monomers of which polyvinylpyrrolidone, polyvinylmethylether, polyacrylic acid and polymethacrylic acid, polyacrylamide, polyethylene oxide, and polyethyleneimine are representative.
All thickeners do not work with equal effectiveness in this invention. Preferred aqueous thickening agents are those which are extremely pseudoplastic (non-Newtonian, rapid relaxation), tend not to develop rigid three-dimensional structure from interpolymer interactions, have a low or negligible viscoelastic character and possess a high gel strength. Such rheological properties are manifested in a composition which has a smooth flowing appearance, is easy to pour and apply, coats uniformly without forming muscilage streamers as the applicator is withdrawn and remains firmly in place without significant sag. Examples of preferred rheology modifiers are xanthan gum and hydroxyalkylcelluloses.
Generally, the concentration of thickener used in the present invention will be dictated by the method of application. Spraying or misting requires a lower composition viscosity for easy and effective application of treatment than dipping. Film forming barrier dips typically require high apparent viscosity necessary to form thick coatings which insure improved prophylactic effect.
Additional film forming agents are included which typically work in conjunction with thickeners. In fact, many of the aforementioned rheology modifiers are themselves film formers of greater or lesser effectiveness; however, a preferred grade of polyvinyl alcohol when used with preferred thickeners such as xanthan gum or hydroxyalkylcelluloses affords particularly useful properties to compositions of this teaching, most notably the development of xe2x80x9cbalancedxe2x80x9d films which are sufficiently water-sensitive to be stripped off with conventional washing, but capably adherent to withstand premature loss of integrity between applications. The success of the barriers thus formed by compositions of this invention are, in part, a consequence of a hydrophobic-hydrophilic balance, caused when non-volatile ingredients, especially fatty acids, surfactants and hydrotropes, become resident throughout the film and whose individual properties become additive with those characteristics of the thickeners and film formers. Such inclusions also plasticize the film and render it pliable.
Polyvinyl alcohol is a polyhydroxide polymer having a polymethylene backbone with pendent hydroxy groups. The monomer does not exist, so the polyvinyl alcohol moiety is made by first forming polyvinyl acetate and removing acetate groups using a base catalyzed methanolysis. Polyvinyl acetate polymerization is accomplished by conventional processes and the degree of hydrolysis is controlled by preventing completion of the methanol reaction. Variation of film flexibility, water sensitivity, ease of salvation, viscosity, film strength and adhesion can be varied by adjusting molecular weight and degree of hydrolysis. The preferred polyvinyl alcohol for use in compositions herein has a degree of hydrolysis greater than 92%, preferably greater than 98%, most preferably greater than 98.5%; and, has a molecular weight that falls in the range of between about 15,000 and 100,000, but preferably between 40,000 and 70,000 corresponding to a solution viscosity (4% wt aqueous solution measured in centipoise (cP) at 20xc2x0 C. by Hoeppler falling ball method) of 12-55 cP (0.012 to 0.055 Paxc2x7s) and 12-25 cP (0.012 to 0.025 Paxc2x7s)respectively.
Treatment of inanimate objects can be accomplished by spraying or wiping a use solution onto the object or surface. An object can also be treated via submersion into an adequate supply of the use solution, which is typically an aqueous solution containing a major proportion of water and an effective amount of an antimicrobial or antiviral complex. The use solution can also contain one or more film forming agents to prevent excessively rapid shedding of the treatment solution. Volumes of water, such as those found in swimming pools, water cooling towers and food process and transport streams, can be treated by addition of the complex (either made in-situ or pre-made via non-aqueous routes) to a concentrated liquid, gel, aerosol, solid, or powder to the water. Addition can take place within the main volume of water, or can occur within a makeup stream of fresh water being added to the main volume. Non-aqueous medium (such as oils or plastics) can be treated using an in-situ complex, or by incorporation of a pre-made complex.
It is believed that use solutions contain effective amounts of a poly-halogen complex which forms, in-situ, from the combination of a quaternary or protonizable nitrogen source, an oxidant and a halide source.
Additionally, microbial and viral control of gaseous (especially air) or liquid streams can be affected by the incorporation of effective amounts of a poly-halogen complex deposited onto a filtering substrate.
Microbial or viral populations on surfaces, objects, gaseous streams, and bodies of water can be reduced by applying thereto an effective amount of a complex of the formula 
wherein Rxe2x80x2, Rxe2x80x3, Rxe2x80x3 and Rxe2x80x2xe2x80x3 are each independently a straight or branched, saturated or unsaturated, hydrocarbon group of 1 to 24 carbon atoms, in which the hydrocarbon group is unsubstituted or substituted by hydroxyl, carboxyl, or alkylamido, or in which the hydrocarbon group is uninterrupted or interrupted by a heteroatom; an aryl group, or aralkyl group in which alkyl has 1 to 4 carbon atoms; u is an integer from 0 to 1; w is an integer from 1 to 8; y and y1 are each independently integers from 0 to 8; z is an integer from 0 to 1, and V is a non-halogen anion, except hydroperoxy, such as, for example, sulfate, methylsulfate, ethylsulfate, borate, phosphate, carbonate, silicate, tartrate, acetate, citrate, and the like. Preferably, y, y1 and z can be 0.
Another useful complex is of the formula 
wherein W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-6 carbon atoms;
Rb is R4xe2x80x94COxe2x80x94NH in which R4 is a saturated or unsaturated, branched or linear hydrocarbon group having 4-22 carbon atoms, or R4;
R1 is hydrogen, A or (Anxe2x80x94Wxe2x80x94CO2xe2x88x92M+ in which A is a linear or branched alkyl, hydroxyalkyl or alkoxyalkyl having 1-4 carbon atoms, n is an integer from 0 to 6, and M+ is an alkali metal cation, a hydrogen ion or an ammonium cation;
R2 is (A)nxe2x80x94Wxe2x80x94CO2xe2x88x92M+;
R3 is hydrogen or A; and V, u, w, y, y1 and z are as previously defined.
Another effective complex is an acidified amine oxide of the formula 
wherein R10, R11, and R12 are each independently hydrogen, or at least one straight or branched alkyl group of 1 to 16 carbon atoms, in which alkyl is unsubstituted or substituted by hydroxyl, carboxyl, or alkylarnido, or in which alkyl is uninterrupted or interrupted by a heteroatom; an aryl group, or aralkyl group in which alkyl has 1 to 4 carbon atoms; and V, u, w, y, y1 and z are as previously defined.
Yet another useful complex is of the formula 
wherein Z is CO2H, SO3H, OSO3H, or OPO3H; W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-6 carbon atoms;
Ra is a linear or branched alkyl, hydroxyalkyl or alkoxyalkyl group having 6-22 carbon atoms; or R4xe2x80x94COxe2x80x94NH(CH2)xxe2x80x2 in which R4 is a saturated or unsaturated, branched or linear alkyl group having 4-22 carbon atoms, and xxe2x80x2 is an alkylene group having 1-6 carbon atoms; and V, u, w, y, y1 and z are as previously defined.
Another useful complex is of the formula: 
wherein R1, R2 and R3 are each, independently, H or xe2x80x94A1xe2x80x94Y in which A1 is a C7 to C20 saturated or unsaturated, linear or branched alkylene group, and Y is H, NH2, OH or COOM1 in which M1 is H or a Group I metal ion; B is a C1 to C20 saturated or unsaturated, linear or branched chain alkylene group, and Y1 is H, NH2, OH, COOM2 or xe2x80x94NHxe2x80x94CORq in which M2 is H or a Group I metal ion and Rq is a C1 to C20 saturated or unsaturated, linear or branched chain alkyl group; R5 is H or a C1 to C3 alkyl group at one of the nitrogen atoms; and V, u, w, y, y1, and z are as previously defined.
Another useful complex is of the formula 
wherein R10, R11, and R12 are each, independently, hydrogen or at least one straight or branched, saturated or unsaturated, hydrocarbon group of 1 to 24 carbon atoms, in which hydrocarbon is unsubstituted or substituted by hydroxyl, carboxyl, or alkylamido, or in which hydrocarbon chain is uninterrupted or interrupted by a heteroatom; an aryl group, or aralkyl group in which alkyl has 1 to 4 carbon atoms; and V, u, w, y, y, and z are as previously defined.
Another useful complex is of the formula 
wherein Ra is a linear or branched, saturated or unsaturated, alkyl, hydroxyalkyl or alkoxyalkyl group having 1-22 carbon atoms; Rb is H or CH3; W is a linear or branched alkylene, hydroxyalkylene or alkoxyalkylene group having 1-4 carbon atoms, and V, u, w, y, y1 and z are as previously defined.
Another useful complex is of the formula 
wherein Rd is a common moiety as part of a natural amino acid; e.g., H, alkyl, hydroxyalkyl, thioalkyl, alkyl-aryl, carboxyl, amido, alkyl-amino, and the like, and V, u, w, y, y1 and z are as previously defined.
Another useful complex is of the formula
[poly-peptide]acidified+ (VuIwBryCly1Fz)xe2x88x92
[poly-peptide]acidified+ refers to an acidified protein, and V, u, w, y, y1, and z are as previously defined.
The invention also involves methods of treating skin diseases in, or on, mammals. If a short application is sufficient, a use solution can be sprayed or wiped onto an animal. Alternatively, the animal can be dunked into the use solution. If a longer residence time is required, the use solution can contain one or more film forming agents to slow down shedding of the treatment solution. If treating humans, the use solution can typically include a cream or lotion which can be applied to the skin and left in place. The antimicrobial or antiviral complexes described herein can be added to any suitable carrier, including hand lotions and the like. These same complexes and formulations can also be used to treat non-skin surfaces which might come in contact with the skin surfaces (e.g., bandages, gloves, breathing masks.
These methods include applying to the skin of said mammal an effective amount of a particular complex. One such useful complex is of the formula 
wherein Rxe2x80x2, Rxe2x80x3, Rxe2x80x3 and Rxe2x80x2xe2x80x3, V, u, w, y, y1 and z are as previously defined.
Another useful complex is of the formula 
wherein W, Rb, R1, R2, V, u, w, y, y1 and z are as previously defined.
Another effective complex for treating skin diseases of mammals is of the formula 
wherein R10, R11, and R12, V, u, w, y, y1 and z are as previously defined. In one embodiment, Rxe2x80x2 and Rxe2x80x3 are each methyl and R is a C8-C12 alkyl group. Alternatively, Rxe2x80x2, and Rxe2x80x3 are each methyl and R is a C8-C12 alkyl group.
Yet another effective complex is of the formula 
wherein Z, W, Ra, V, u, w, y, y1 and z are as previously defined.
Another effective complex is of the formula 
wherein:
R1, R2, R3, B, Y1, Rq, R5, V, u, w, y, y1, and z are as previously defined.
Another effective complex for treating skin diseases of mammals is of the formula 
wherein R10, R11, R12, V, u, w, y, y1, and z are as previously defined.
Especially useful complex is of the formula 
wherein Ra, Rb, W, V, u, w, y, y1, and z are as previously defined.
Likewise, another useful complex for treatment of skin is of the formula 
wherein Rd, V, u, w, y, y1, and z are as previously defined.
And another useful complex is of the formula
[poly-peptide]acidified+ (VuIwBryCly1Fz)xe2x88x92
wherein [poly-peptide]acidified+, V, u, w, y, y1, and z are as previously defined.
In the above complexes, a preferred embodiment is a complex where y, y1, and z are 0.